In PUPs with severe haemophilia A, octanate demonstrated haemostatic efficacy with a low rate of inhibitor development.

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Background: The SIPPET study investigated inhibitor development in 251 previously untreated patients (PUPs) treated with either plasma-derived FVIII products containing von Willebrand factor (pdFVIII/VWF; n = 125), or recombinant FVIII (rFVIII; n = 126) from hamster cell lines. Amongst PUPs with non-null F8 mutations, none developed inhibitors when treated with pdFVIII/VWF while the cumulative inhibitor incidence was 43% in those treated with hamster-cell-derived rFVIII. In patients with null F8 mutations, the cumulative inhibitor incidences were 31% and 47% in patients treated with pdFVIII/VWF and rFVIII, respectively. In patients with null mutations the cumulative incidences of high-titre inhibitors were 22% and 30% with pdFVIII/VWF and rFVIII, respectively. Aim: To investigate the relationship between inhibitor development and F8 mutation type in PUPs with severe hemophilia A treated with either a rFVIII from a human cell line (Nuwiq®; simoctocog alfa) or either of two pdFVIII/VWF products, one with a VWF/FVIII ratio of 0.4 (octanate®) the other with a VWF/FVIII ratio of 1.0 (wilate®). Materials and Methods: Data from completed multicenter, prospective trials with octanate® and wilate® and interim data from the NuProtect study with Nuwiq® were analyzed. Data on F8 mutation type were available for 50/51, 27/28 and 58/66 patients in each of the studies. All patients in the three studies had no previous treatment with FVIII concentrates or other blood products containing FVIII. Results: In the three studies, 18% (9/50), 7.4% (2/27) and 19%.0% (11/58) of patients had non-null mutations. None of the patients with non-null mutations developed inhibitors with octanate®, wilate® or Nuwiq®. In patients with null mutations, 9.8% (4/41), 12.0% (3/25), and 17.0% (8/47) developed high-titre inhibitors. Conclusions: PUPs with non-null F8 mutations did not develop inhibitors when treated with octanate®, wilate® or Nuwiq®. Whilst the different studies are not directly comparable, the findings with these products, two pdFVIII/VWF and a rFVIII from a human cell line, show similar behavior to the SIPPET trial where no patients with non-null mutations treated with pdFVIII/VWF products developed inhibitors. Disclosures Liesner: Bayer: Consultancy, Research Funding; Baxalta: Consultancy, Research Funding; Novo Nordisk: Research Funding, Speakers Bureau; Roche: Research Funding; Sobi: Speakers Bureau; Octapharma: Consultancy, Other: Clinical study investigator for NuProtect Study (Octapharma sponsored), Research Funding, Speakers Bureau. Versteden:Octapharma AG: Employment. Lowndes:Octapharma AG: Employment. Belyanskaya:Octapharma AG: Employment. Oldenburg:Grifols: Honoraria, Research Funding; Novo Nordisk: Honoraria, Research Funding; Biotest: Honoraria, Research Funding; Biogen: Honoraria, Research Funding; Pfizer: Honoraria, Research Funding; Roche: Honoraria, Research Funding; Octapharma: Honoraria, Research Funding; Shire: Honoraria, Research Funding; CSL Behring: Honoraria, Research Funding; Bayer: Consultancy, Honoraria, Research Funding; Chugai: Honoraria, Research Funding; Swedish Orphan Biovitrum: Honoraria, Research Funding. Pavlova:Novo Nordisk: Honoraria; Octapharma: Honoraria.

Background Immune tolerance induction (ITI) with repeated factor VIII (FVIII) administration is the only strategy proven to eradicate inhibitors. The observational ITI study is evaluating ITI with a range of FVIII products. Methods This subgroup analysis reports prospective interim data for patients treated with a plasma-derived, von Willebrand factor-stabilized FVIII concentrate (pdFVIII/VWF, octanate). Complete success (CS) of ITI required achievement of three criteria: inhibitor titer < 0.6 BU/mL; FVIII recovery ≥ 66%; FVIII half-life ≥6 hours. Partial success (PS) required achievement of two criteria and partial response (PR) one. ITI success was defined as CS or PS. Data were analyzed for patients who achieved CS, had 36 months' observation, or failed ITI. Results One-hundred prospectively enrolled patients were included in the analysis; 91 had poor prognosis factors for ITI success. The mean (standard deviation) daily ITI dose was 116.4 (61.1) IU FVIII/kg in 14 low responders (< 5 BU/mL) and 173.7 (112.0) IU FVIII/kg in 86 high responders (≥ 5 BU/mL). Inhibitor titers < 0.6 BU/mL were achieved in 71% of patients in a median of 4.01 months, accompanied by a 93% reduction in bleeding rate. ITI success was achieved by 70% of patients and 56 of 72 (78%) primary (first-line) ITI patients. PR was achieved by 5 patients; ITI failed in 25 patients. PS and CS were achieved in a median of 5.55 and 11.25 months, respectively. Conclusions ITI with pdFVIII/VWF led to rapid eradication of FVIII inhibitors, normalization of FVIII pharmacokinetics in the majority of patients, and a significant reduction in bleeding rates.